Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

Chromophobe Renal Cell Carcinoma

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Part 1: nivolumab 240mg IV q2w for a maximum of 12 months.

Part 2; nivolumab 240mg IV q3w in addition to ipilimumab 1mg/kg q3w x 4 cycles Then nivolumab 240mg q2w for a maximum of 12 months.

Dosage Form: Nivolumab BMS-936558-01 Solution for Injection Potency: 100 mg (10 mg/mL) Primary Packaging: 10 mL vial Appearance: Clear to opalescent colourless to pale yellow liquid. May contain particles.

Storage Condition: 2 to 8°C. Protect from light and freezing.

Dosage Form: Ipilimumab Solution for Injection Potency: 200 mg (5 mg/mL) Primary Packaging: 40 mL vial Appearance: Clear, colourless to pale yellow liquid. May contain particles. Storage Condition: 2 to 8°C. Protect from light and freezing.

This study aims to evaluate the safety, tolerability and effectiveness of new treatments for kidney cancer called Nivolumab and Ipilimumab. The study is in two parts; in the first instance patients receive nivolumab alone. If this treatment is not effective patients may move onto the second part of the trial, where they receive nivolumab + ipilimumab. There is no placebo.

The reason to offer one treatment alone, followed by two treatments together is that it is thought that the double treatment may have more side-effects, but also may be effective in people in whom the single first treatment (nivolumab alone) has not helped.

Nivolumab and ipilimumab are experimental treatments. This means that they are not an approved treatment for non-clear cell kidney cancer in Australia.

The purpose of this study is to test the effectiveness, safety, and tolerability of Nivolumab (also known as Opdivo or BMS-936558) and Ipilumumab (also known as MDX-010 or Yervoy). Nivolumab and ipilimumab are antibodies (a type of human protein) that are being tested to see if they will allow the body's immune system to work against tumour cells. The immune system is the body's defence against cancer, bacteria and viruses. The effectiveness of nivolumab and ipilimumab in cancer of the kidney will be assessed by measuring the size of patient tumours via CT scans.

Nivolumab and ipilimumab have been used alone or in combination in many other cancers, and are licenced for use in other cancers like advanced melanoma and bladder cancer in Australia. They have not been tested in people with non-clear cell kidney cancer.

About 85 participants with non-clear cell kidney cancer are expected to participate in this study, from Australia and New Zealand.

This research study has been initiated by Dr. Craig Gedye, is being conducted in collaboration with the Centre for Biostatistics and Clinical Trials (BaCT) and sponsored in Australia by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Pty Ltd. Bristol Myers Squibb (BMS) is supplying the study drugs and grant funding for this research.

Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602)

A Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602).

This is defined as the proportion of participants in the analysis set with a confirmed complete response (CR) or partial response (PR) divided by the number of participants in the analysis set.

Measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that progressive disease is objectively documented.

For Part 1, PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death, whichever occurs first. For Part 2, PFS is defined as the interval from date of progressive disease on nivolumab monotherapy until the date of first evidence of disease progression or death, whichever occurs first.

Defined as the proportion of participants in the analysis set with an immune related complete response (irCR), or immune related partial response (irPR), divided by the number of participants in the analysis set.

For Part 1, irDCR6 is defined as an assessment of CR or iPR or iSD according to modified irRECIST. For Part 2, irDCR6 is defined in the same way except that the extent of disease defining the baseline tumour burden is measured at the date of disease progression on nivolumab monotherapy.

Overall survival (OS) is defined as the time between the date of registration to part 1 of the study and the date of death due to any cause.

Bristol-Myers Squibb

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Pembrolizumab

Axitinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Axitinib will be administrated orally 5 mg twice a day, with a dose adaptations to the manufacturer recommendations in both groups. Doses can be increased up to 10 mg twice daily.

Pembrolizumab will be administrated intravenously (IV) over 30 minutes at the dose of 200 mg every 3 weeks according to recent summary of product characteristics (SPC) together with axitinib.

Axitinib will be administrated orally 5 mg twice a day, with a dose adaptations to the manufacturer recommendations in both groups. Doses can be increased up to 10 mg twice daily.

Axitinib Oral Tablet [Inlyta]

Pembrolizumab intravenously over 30 min minutes at 200 mg every 3 weeks

Pembrolizumab Injection [Keytruda]

Sylvie NEGRIER

Remy DELVA, MD

Fabien CALCAGNO, MD

Marine GROSS-GOUPIL, MD

Hakim MAHAMMEDI, MD

Gwenaelle GRAVIS-MESCAM, MD

Delphine BORCHIELLINI, MD

Stéphane OUDARD, PhD

Fréderic ROLLAND, MD

Christine CHEVREAU, MD

Lionnel GEOFFROIS, MD

Laurence ALBIGES, MD

Sylvie NEGRIER, PhD

Multicenter Phase II Study of Axitinib +/- Pembrolizumab in First Line Treatment for Patients With Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (PRCC)

Papillary renal cell carcinoma (PRCC) is the second most common subtype of renal carcinoma accounting for approximatively 10-15% of all renal cancers. Different types of PRCC have been described on the basis of two histologic subtypes, type 1 in 25 to 30% cases, and type 2, with a worse prognosis reported for type 2 metastatic disease. There is currently no standard of care specifically dedicated to metastatic PRCC patients (mPRCC) and treatments developed for metastatic clear cell carcinomas are commonly used ; therefore, mPRCC enrollment in clinical trials is encouraged.

Clinical trials investigated treatments such as sunitinib, or everolimus approved for advanced clear cell carcinoma, or the dual kinase inhibitor directed both towards VEGF receptors (VEGFr) and the MET pathway foretinib, or more recently, the selective MET inhibitor savolitinib. Response rates (RR) were disappointing since generally below 15%, except in a subset of patients with MET germline alterations.

Axitinib which is indicated as second-line treatment in advanced clear cell carcinoma was investigated in a recent specific trial : the Axipap trial. This multicentric phase II trial was conducted after central pathology review to confirm the histologic subtype and a central review was performed to assess the primary endpoint : the 24 week progression free rate (24wPFR). With a median follow up time of 30 months this 24wPFR was found to be over 45%. The best response rate was 28.6% according to the investigators with a median duration of response near 8 months. The investigator assessed response rate was 35.7% in the type 2 subgroup indicating a more important effect of anti-VEGFr in this subtype than in the type 1. The median PFS was around 6 months and was virtually identical in both subtypes.

Recently, some preliminary results of the use of Immune Checkpoint Inhibitors in metastatic non clear cell carcinoma were made available. The PD1 directed antibody Pembrolizumab showed a 28% response rate in 118 patients with papillary tumors including a 6% complete remission rate ; the median duration of response was of 15.3 \[2.8-21.0+\] months. Atezolizumb (anti-PDL1) combined with Bevacizumab and Durvalumab (anti-PDL1) combined with savolitinib (Met directed TKI) obtained response rates in the same range. These preliminary results demonstrated the potential interest of combining axitinib with an immune check point inhibitor. The results of pembrolizumab as monotherapy were obtained in the largest subset with mPRC.

According to these results obtained, the combination of axitinib and pembrolizumab seems promising in type 2 papillary tumors.

Multicenter, randomized, prospective, phase II study

Axitinib +/- Pembrolizumab in First Line Treatment of mPRCC

6-month objective response rate (6m-ORR), defined as the proportion of patients with CR or PR at 6 months

Duration of response in each arm, calculated from the date of first documented response to the date of first documented progression or death.

Best overall response in each arm, defined as the best response according to RECIST v1.1 recorded from baseline until the end of the study (treatment).

PFS in each arm, defined as the time from the date of first treatment administration to the date of documented progression or death from any cause.

OS in each arm, defined as the time from the date of first treatment administration to the date of death from any cause.

Safety profile, determined using NCI CTC-AE grading scale v5

Centre Leon Berard

Immunomodulating Agents

Cabozantinib 60 mg/day for up to 12 cycles (one cycle is 28 days), taken orally

The 20 mg cabozantinib drug product is a film-coated, white, round, immediate-release tablet. Cabozantinib should not be stored above 25°C (77°F).

Cabozantinib

Deepti Pandey

Margaret McJannett

Craig Underhill

Jacqui McBurnie

Felicia Roncolato, MBBS

Suma Santosh

Carole Harris

Mary Gozer

Howard Gurney

Radhika Butala

Craig Gedye

kim adler

Jeffrey Goh

Annette Cubitt

Ganessan Kichenadasse

Alison Richards

Francis Parnis

Helen Daykin

Ian Davis

Lauren Mitchell

David Pook

Karen Gillett

Javier Torres

David Pook, MBBS FRACPMD

Renal cell carcinoma (RCC) is the 9th most common cancer in Australia, the 10th most common cancer in Western populations.\~75% of kidney cancers are clear-cell renal cell carcinomas (ccRCC). Many patients present with advanced or unresectable disease at diagnosis and a number of treatments are now available for metastatic ccRCC included vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs), mTOR inhibitors, and cytokines. More recently first line use of immunotherapy demonstrated improved survival with checkpoint inhibitors. While many patients benefit from first-line treatment, progression is inevitable and these treatments remain on the whole palliative. Second-line VEGFR TKIs, mTOR inhibitors and immunotherapy have some benefit but in a smaller increment than first-line treatment.

While \~75% of kidney cancers are the clear-cell variant, \~25% of kidney cancers are non-clear cell histology (nccRCC) and include papillary, chromophobe, sarcomatoid, collecting duct carcinoma, Xp11 translocation carcinoma and unclassified. Patients with non-ccRCC have significantly lower response rates and poorer median progression-free survival and overall survival than those with ccRCC. Non clear cell histologies have largely been excluded from large phase III randomised clinical trials and therefore the optimal treatment and sequencing of therapies for these patients remains unclear.

Despite recent unprecedented advances in treatment, there continues to be an unmet need to improve outcomes for patients with previously untreated, unresectable or metastatic renal cell carcinoma. This is particularly relevant in non-clear cell RCC. Because it is a rarer subtype of metastatic renal cell carcinoma, it is more challenging to study, and treatment efficacy data is sparse.

The research project is testing a new treatment for participants with locally advanced or metastatic non-clear cell kidney cancer. The new treatment involves a drug called Cabozantinib (also known as Cabometyx). This drug has been used previously in many cancers, including clear cell kidney cancer and thyroid cancer.

The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of Cabozantinib. Cabozantinib is a anti-cancer drug that works by blocking cancer cell growth. It blocks particular proteins called protein kinases on cancer cells. Protein kinases encourage the cancer to grow. Cabozantinib is called a multi kinase inhibitor because it blocks a number of these proteins. How well cabozantinib works in cancer of the kidney will be tested by measuring the change in size of your tumours that are seen on CT scans.

Cabozantinib is approved to treat clear cell kidney cancer and thyroid cancer in Australia. It has not been tested in people with non-clear cell kidney cancer.

About 48 participants with non-clear cell kidney cancer are expected to participate in this study, from Australia. Even though this study may be suitable for you, it is possible that you may not be enrolled in this study.

This research study has been initiated by Dr. David Pook, is being conducted in collaboration with the Centre for Biostatistics and Clinical Trials (BaCT) and sponsored in Australia by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Pty Ltd. Ipsen is supplying

ANZUP - Non-clear Cell Post Immunotherapy CABozantinib (UNICAB)

A Phase II of Single Agent Cabozantinib in Patients With Locally Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma Post Immunotherapy or Who Are Unsuitable for Immunotherapy (ANZUP1802)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602)	NCT03177239	Renal Cell Carc... Papillary Renal... Papillary Renal... Chromophobe Ren... Sarcomatoid Ren... Xp11 Translocat...	Nivolumab Ipilimumab	18 Years -	Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602)	NCT03177239	Renal Cell Carc... Papillary Renal... Papillary Renal... Chromophobe Ren... Sarcomatoid Ren... Xp11 Translocat...	Nivolumab Ipilimumab	18 Years -	Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Axitinib +/- Pembrolizumab in First Line Treatment of mPRCC	NCT05096390	Papillary Renal...	Axitinib Oral T... Pembrolizumab I...	18 Years -	Centre Leon Berard
ANZUP - Non-clear Cell Post Immunotherapy CABozantinib (UNICAB)	NCT03685448	Renal Cell Carc... Papillary Renal... Papillary Renal... Chromophobe Ren... Sarcomatoid Ren... Xp11.2 Transloc...	Cabozantinib	18 Years -	Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602)	NCT03177239	Renal Cell Carc... Papillary Renal... Papillary Renal... Chromophobe Ren... Sarcomatoid Ren... Xp11 Translocat...	Nivolumab Ipilimumab	18 Years -	Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Spots Global Cancer Trial Database for papillary renal cell carcinoma type 2